Download Cell Cycle Checkpoints

Events of The Cell Division Cycle Occur in a Particular Order
Entering Mitosis Before the Completion of S phase is
Bad for Chromosomes and Therefore Bad for Cells
Cell Cycle Checkpoints
G1
Elledge, Science 274:1664 (1996)
Substrate-Product versus Extrinsic Control Mechanisms
Weinert and Hartwell, Science 246:629 (1989)
Caffeine Abrogates the Replication Checkpoint
Molecular Biology of the Cell © 1994 by Bruce Alberts et al
rad9 is the First Cell Cycle Checkpoint Mutant
0 hrs at res temp
3 hrs at res temp
cdc9
(DNA ligase)
cdc9 rad9
Weinert and Hartwell, Science 246:629 (1989)
Cell Cycle Checkpoints Improve Cell Viability
Weinert and Hartwell, Science 246:629 (1989)
Cell Cycle Checkpoints
G1
Why always negative regulation?
A Mechanism Involving Negative Regulation is More Robust
Very different
situations
Anaphase:
Not very
different
situations
Anaphase:
GO x 5
GO x 6
How do Cell Cycle Checkpoints Work?
G1
How do Cell Cycle Checkpoints Work?
Zhou and Elledge Nature 408, 433 - 439 (2000)
Replication and Damage Checkpoints in Yeast
Elledge, Science 274:1664 (1996)
Inhibitory CDC2 Phosphorylation
is a kinase
is a phosphatase
G2 Arrest Induced by DNA Damage
Signal
Sensor
Transducer
Effector
Cytoplasm
Nucleus
Metaphase in a mammalian cell
The Metaphase to Anaphase Transition
(also called the cyclosome
NOT the tumor suppressor!!)
The Spindle Assembly Checkpoint
The Spindle Assembly Checkpoint
Mitotic Checkpoint Complex (MCC)
Bub1
Mad2
BubR1
Bub3
CDC20
Mitotic Defects Leading to Aneuploidy
Weaver BA, Cleveland DW. Does aneuploidy cause cancer? Curr Opin Cell Biol. 2006 Dec;18(6):658-667.
Spindle Assembly Checkpoint Genes that are Mutated
and/or Misregulated in Human Cancers
Weaver BA, Cleveland DW. Does aneuploidy cause cancer? Curr Opin Cell Biol. 2006 Dec;18(6):658-667.
Chi and Jeung, J. Cell. Biochem. 102:531 (2007)